Objective:To investigate the potential anti-aging mechanism of9-hydroxy-6,7-dimethoxydalbergiquinol(HDDQ)on hydrogen peroxide(H2O2)-induced oxidative stress in human dermal fibroblasts(HDFs).Methods:The effect of HDDQ...Objective:To investigate the potential anti-aging mechanism of9-hydroxy-6,7-dimethoxydalbergiquinol(HDDQ)on hydrogen peroxide(H2O2)-induced oxidative stress in human dermal fibroblasts(HDFs).Methods:The effect of HDDQ on cell viability was assessed by MTT assay,and the effects of HDDQ on senescence-like phenotypes were determined by senescence-associatedβ-galactosidase(SA-β-gal)staining,Western blotting analysis,and a cell proliferation assay.The expression level and activity of sirtuin-1(SIRT1)induced by HDDQ were also measured.Results:HDDQ reversed senescence-like phenotypes in the oxidant-challenged model,through reducing SA-β-gal activity and promoting cell growth.Meanwhile,decreases in ac-p53,p21Cip1/WAF1,and p16Ink4a and an increase in p Rb were observed.HDDQ induced the expression of SIRT1 in a concentration-and time-dependent manner.Moreover,HDDQ inhibited H2O2-induced phosphorylation of Akt by SIRT1 up-regulation and reduced SA-β-gal staining.Conclusions:HDDQ inhibits H2O2-induced premature senescence and upregulation of SIRT1 expression plays a vital role in the inhibition of the senescence phenotype in HDFs.展开更多
Breast cancer is a complex and heterogeneous disease with different clinical outcomes. The investigations of new biomolecular markers are essential to know the prognosis and improve the clinical management of patients...Breast cancer is a complex and heterogeneous disease with different clinical outcomes. The investigations of new biomolecular markers are essential to know the prognosis and improve the clinical management of patients. The SIRT-1 （sirtuin- 1） is a histone deacetylase implicated in various epigenetic critical functions for the cells and the maintenance of genomic stability. The objective of this study is to investigate the grade of expression of the SIRT-I （sirtuin-1） and the prognostic value in overall survival of women with breast cancer. Retrospective cohort of 457 women with breast cancer has been researched, undergoing treatment in Erechim-RS from 2003 to 2013 and followed until July 2015. The degree of SIRT-1 expression was investigated by immunohistochemistry in 123 patients （26.9%） of the cohort. The OS （overall survival） from specific disease and risk of death from breast cancer were estimated by Kaplan-Meier and Cox＇s proportional risks. The median age of 57.4 years cohort with OS of 79.6% in 5 years and 69.1% at 10 years, with follow-up time of 61.9 months are revealed in this work. The SIRT-1 overexpression was found in 6.5% of cases and characterized a subgroup of women with shorter survival and increased risk of death from breast cancer （HR = 2.66; 95% CI 1.03 to 6.86; p = 0.043） and adjusted by age （HR = 2.86; 95% CI 1.11 to 7.38; p = 0.030）, histology （HR = 2.79; 95% CI 1.07 to 7.28; p = 0.036）, lymph nodes （HR = 2.73; 95% CI 1.06 to 7.04; p = 0.037）, Her-2 （HR = 2.82; 95% CI 1.07 to 7.44; p = 0.036）; chemotherapy （HR = 2.90; 95% CI 1.11 to 7.60; p = 0.030） and radiotherapy （HR = 2.71; 95% CI 1.05 to 7.01; p = 0.040）. In regressive multivariate models adjusted for age, status of axillary lymph nodes, Her-2 expression and proliferation index （Ki-67）, the grade of expression of the SIRT-1 maintained association with poor prognosis. From the study, it can be concluded that the assessment of the SIRT-1 expression is an independent prognostic biomarker in breast cancer.展开更多
Obesity, especially at mid-life, is a major risk factor for atherosclerosis, insulin resistance and the metabolic syndrome, which in turn contribute to coronary artery disease (CAD), Type 2 diabetes and Alzheimer’s d...Obesity, especially at mid-life, is a major risk factor for atherosclerosis, insulin resistance and the metabolic syndrome, which in turn contribute to coronary artery disease (CAD), Type 2 diabetes and Alzheimer’s disease (AD). The rise in overweight and obesity in all societies is prompting intense research into the causes and effects of the condition. Obesity disrupts many body systems including glucose and lipid metabolism, circadian rhythms and liver function. It also causes or increases inflammation and oxidative stress. Within cells, the endoplasmic reticulum (ER) appears to be particularly susceptible to such metabolic disruption. Sirtuin 1?(Sirt1) and leptin have received attention recently as they are central regulatory factors for the body’s metabolic pathways which interact at particular levels, for example lipid and Abeta metabolism. This mini-review discusses recent findings concerning obesity, lipid metabolism and the role of Sirtuin 1 and how all influence the ER. A greater understanding of obesity and its effects on metabolic control systems of the body are required, to develop pharmacological, dietary and lifestyle changes that will reduce the incidence of CAD, Type 2 diabetes and AD.展开更多
Synaptic dysfunction and abnormal processing of amyloid precursor protein(APP) are early pathological features in Alzheimer’s disease(AD). Recently, noncoding RNAs such as micro RNAs(mi RNAs) and circular RNAs(circ R...Synaptic dysfunction and abnormal processing of amyloid precursor protein(APP) are early pathological features in Alzheimer’s disease(AD). Recently, noncoding RNAs such as micro RNAs(mi RNAs) and circular RNAs(circ RNAs) have been reported to contribute to the pathogenesis of AD. We found an age-dependent elevation of mi R-138 in APP/PS1(presenilin-1) mice. Mi R-138 inhibited the expression of ADAM10 [a disintegrin and metalloproteinase domain-containing protein 10], promoted amyloid beta(Ab) production, and induced synaptic and learning/memory deficits in APP/PS1 mice, while its suppression alleviated the AD-like phenotype in these mice. Overexpression of sirtuin 1(Sirt1), a target of mi R-138, ameliorated the mi R-138-induced inhibition of ADAM10 and elevation of Ab in vitro. The circ RNA HDAC9(circ HDAC9) was predicted to contain a mi R-138 binding site in several databases. Its expression was inversely correlated with mi R-138 in both Ab-oligomertreated N2 a cells and APP/PS1 mice, and it co-localized with mi R-138 in the cytoplasm of N2 a cells. Circ HDAC9 acted as a mi R-138 sponge, decreasing mi R-138 expression, and reversing the Sirt1 suppression and excessive Ab production induced by mi R-138 in vitro. Moreover,circ HDAC9 was decreased in the serum of both AD patients and individuals with mild cognitive impairment.These results suggest that the circ HDAC9/mi R-138/Sirt1 pathway mediates synaptic function and APP processing in AD, providing a potential therapeutic target for its treatment.展开更多
文摘Objective:To investigate the potential anti-aging mechanism of9-hydroxy-6,7-dimethoxydalbergiquinol(HDDQ)on hydrogen peroxide(H2O2)-induced oxidative stress in human dermal fibroblasts(HDFs).Methods:The effect of HDDQ on cell viability was assessed by MTT assay,and the effects of HDDQ on senescence-like phenotypes were determined by senescence-associatedβ-galactosidase(SA-β-gal)staining,Western blotting analysis,and a cell proliferation assay.The expression level and activity of sirtuin-1(SIRT1)induced by HDDQ were also measured.Results:HDDQ reversed senescence-like phenotypes in the oxidant-challenged model,through reducing SA-β-gal activity and promoting cell growth.Meanwhile,decreases in ac-p53,p21Cip1/WAF1,and p16Ink4a and an increase in p Rb were observed.HDDQ induced the expression of SIRT1 in a concentration-and time-dependent manner.Moreover,HDDQ inhibited H2O2-induced phosphorylation of Akt by SIRT1 up-regulation and reduced SA-β-gal staining.Conclusions:HDDQ inhibits H2O2-induced premature senescence and upregulation of SIRT1 expression plays a vital role in the inhibition of the senescence phenotype in HDFs.
文摘Breast cancer is a complex and heterogeneous disease with different clinical outcomes. The investigations of new biomolecular markers are essential to know the prognosis and improve the clinical management of patients. The SIRT-1 （sirtuin- 1） is a histone deacetylase implicated in various epigenetic critical functions for the cells and the maintenance of genomic stability. The objective of this study is to investigate the grade of expression of the SIRT-I （sirtuin-1） and the prognostic value in overall survival of women with breast cancer. Retrospective cohort of 457 women with breast cancer has been researched, undergoing treatment in Erechim-RS from 2003 to 2013 and followed until July 2015. The degree of SIRT-1 expression was investigated by immunohistochemistry in 123 patients （26.9%） of the cohort. The OS （overall survival） from specific disease and risk of death from breast cancer were estimated by Kaplan-Meier and Cox＇s proportional risks. The median age of 57.4 years cohort with OS of 79.6% in 5 years and 69.1% at 10 years, with follow-up time of 61.9 months are revealed in this work. The SIRT-1 overexpression was found in 6.5% of cases and characterized a subgroup of women with shorter survival and increased risk of death from breast cancer （HR = 2.66; 95% CI 1.03 to 6.86; p = 0.043） and adjusted by age （HR = 2.86; 95% CI 1.11 to 7.38; p = 0.030）, histology （HR = 2.79; 95% CI 1.07 to 7.28; p = 0.036）, lymph nodes （HR = 2.73; 95% CI 1.06 to 7.04; p = 0.037）, Her-2 （HR = 2.82; 95% CI 1.07 to 7.44; p = 0.036）; chemotherapy （HR = 2.90; 95% CI 1.11 to 7.60; p = 0.030） and radiotherapy （HR = 2.71; 95% CI 1.05 to 7.01; p = 0.040）. In regressive multivariate models adjusted for age, status of axillary lymph nodes, Her-2 expression and proliferation index （Ki-67）, the grade of expression of the SIRT-1 maintained association with poor prognosis. From the study, it can be concluded that the assessment of the SIRT-1 expression is an independent prognostic biomarker in breast cancer.
文摘Obesity, especially at mid-life, is a major risk factor for atherosclerosis, insulin resistance and the metabolic syndrome, which in turn contribute to coronary artery disease (CAD), Type 2 diabetes and Alzheimer’s disease (AD). The rise in overweight and obesity in all societies is prompting intense research into the causes and effects of the condition. Obesity disrupts many body systems including glucose and lipid metabolism, circadian rhythms and liver function. It also causes or increases inflammation and oxidative stress. Within cells, the endoplasmic reticulum (ER) appears to be particularly susceptible to such metabolic disruption. Sirtuin 1?(Sirt1) and leptin have received attention recently as they are central regulatory factors for the body’s metabolic pathways which interact at particular levels, for example lipid and Abeta metabolism. This mini-review discusses recent findings concerning obesity, lipid metabolism and the role of Sirtuin 1 and how all influence the ER. A greater understanding of obesity and its effects on metabolic control systems of the body are required, to develop pharmacological, dietary and lifestyle changes that will reduce the incidence of CAD, Type 2 diabetes and AD.
基金supported by the National Natural Science Foundation of China (81500925)
文摘Synaptic dysfunction and abnormal processing of amyloid precursor protein(APP) are early pathological features in Alzheimer’s disease(AD). Recently, noncoding RNAs such as micro RNAs(mi RNAs) and circular RNAs(circ RNAs) have been reported to contribute to the pathogenesis of AD. We found an age-dependent elevation of mi R-138 in APP/PS1(presenilin-1) mice. Mi R-138 inhibited the expression of ADAM10 [a disintegrin and metalloproteinase domain-containing protein 10], promoted amyloid beta(Ab) production, and induced synaptic and learning/memory deficits in APP/PS1 mice, while its suppression alleviated the AD-like phenotype in these mice. Overexpression of sirtuin 1(Sirt1), a target of mi R-138, ameliorated the mi R-138-induced inhibition of ADAM10 and elevation of Ab in vitro. The circ RNA HDAC9(circ HDAC9) was predicted to contain a mi R-138 binding site in several databases. Its expression was inversely correlated with mi R-138 in both Ab-oligomertreated N2 a cells and APP/PS1 mice, and it co-localized with mi R-138 in the cytoplasm of N2 a cells. Circ HDAC9 acted as a mi R-138 sponge, decreasing mi R-138 expression, and reversing the Sirt1 suppression and excessive Ab production induced by mi R-138 in vitro. Moreover,circ HDAC9 was decreased in the serum of both AD patients and individuals with mild cognitive impairment.These results suggest that the circ HDAC9/mi R-138/Sirt1 pathway mediates synaptic function and APP processing in AD, providing a potential therapeutic target for its treatment.
